Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Analysing and modelling molecular rate variation among nuclear and mitochondrial genomes. My research will have important practical benefits for bioinformaticians and evolutionary biologists, because existing analytical methods will be rigorously tested and new tools will be developed. Australia has a comparatively high concentration of researchers in this field, so my research will foster domestic collaboration and import international expertise. The research will provide important insights int ....Analysing and modelling molecular rate variation among nuclear and mitochondrial genomes. My research will have important practical benefits for bioinformaticians and evolutionary biologists, because existing analytical methods will be rigorously tested and new tools will be developed. Australia has a comparatively high concentration of researchers in this field, so my research will foster domestic collaboration and import international expertise. The research will provide important insights into the rates and patterns of genetic changes associated with domestication, and into variation in evolutionary rates among the primate ancestors of humans. In addition to developing new software, which will be made publicly available, I will develop new evolutionary models to supplement existing software packages. Read moreRead less
Improving access to phylogenomic resources for under-resourced species: a new look at existing tools. This project will have an impact on our understanding of how to most effectively use existing genomic resources to benefit a wider range of species and to better design new genomic resources. By doing so, improved access to genomic resources will be provided to species that currently have few options.
The Origin and Evolution of the Animal Phyla inferred from Analysis of Multiple-Gene Data. Australia has recently begun an extensive research programme in the genomics of our flora and fauna. The enormous amounts of data that emerge from such research are highly complex, but they hold the key to understanding how biological organisms change over time. Our research will untangle that data to answer fundamental, unanswered questions in modern science: How did the animal groups originate? How are ....The Origin and Evolution of the Animal Phyla inferred from Analysis of Multiple-Gene Data. Australia has recently begun an extensive research programme in the genomics of our flora and fauna. The enormous amounts of data that emerge from such research are highly complex, but they hold the key to understanding how biological organisms change over time. Our research will untangle that data to answer fundamental, unanswered questions in modern science: How did the animal groups originate? How are they related to each other? How is biodiversity changing? The answers to these questions and the new analytical tools we will develop will put Australia firmly on the international "map" of Bioinformatics.Read moreRead less
Solving Darwin's dilemma: Molecular analysis of worker sterility in social insects. One of Darwin's greatest puzzles was how natural selection resulted in worker sterility in social insects. We now know from mathematical modelling that a gene that causes sterility in workers can be at a selective advantage if it increases the reproductive success of queens. This project will take the only known gene that causes sterility, 'Anarchy' from honey bees, and determine how this gene evolved. We will de ....Solving Darwin's dilemma: Molecular analysis of worker sterility in social insects. One of Darwin's greatest puzzles was how natural selection resulted in worker sterility in social insects. We now know from mathematical modelling that a gene that causes sterility in workers can be at a selective advantage if it increases the reproductive success of queens. This project will take the only known gene that causes sterility, 'Anarchy' from honey bees, and determine how this gene evolved. We will determine if Anarchy is the same gene that causes sterility in all social insects, or only in honey bees. The project will be at the forefront of international research by providing a molecular perspective to Darwin's greatest dilemma.
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Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of ....Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of pathologies such as Alzheimer's and Parkinson's disease and other diseases that arise from protein mis-folding and aggregation, including myopathies and cataracts. A participation of chaperonins has been implicated in these age-related diseases and demands detailed structural and functional investigations.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.Read moreRead less
Estimating evolutionary time-scales using genomic sequence data: exploiting opportunities and meeting challenges. Genomic data are being produced at a phenomenal rate, enabling detailed investigations of various biological questions. This project will exploit the new opportunities for improving the estimation of evolutionary time-scales, and develop methods and software to address the new challenges that have surfaced.